Polymorphic forms of compounds as prolyl hydroxylase inhibitor, and uses thereof

Abstract

The present invention relates to the polymorphic forms of the compound of Formula (I), preparation thereof including the preparation of intermediates and pharmaceutical compositions, and use of a polymorph above in the treatment of a disease, a disorder or a condition, or in the manufacturing of a medicament for the treatment of a disease, a disorder or a condition.

What is claimed is: 
     
       1. A crystalline form of compound of Formula I, 
       
         
           
           
               
               
           
         
         characterized by having X-ray powder diffraction pattern with peaks at diffraction angles 2θ of approximately 5.9°, 11.0°, 17.6°, 22.6°, 25.9°, and 26.9°±0.2°. 
       
     
     
       2. The crystalline form of  claim 1 , wherein the X-ray powder diffraction pattern further comprises peaks at diffraction angles 2θ of approximately 14.8° and 24.0°±0.2°. 
     
     
       3. The crystalline form of  claim 1 , wherein the X-ray powder diffraction pattern is substantially in accordance with  FIG. 1 . 
     
     
       4. The crystalline form of  claim 1 , characterized by a melting point ranging from about 174° C. to 177° C. 
     
     
       5. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of Formula I, 
       
         
           
           
               
               
           
         
         and at least one pharmaceutically acceptable carrier, wherein at least 85% of the compound of Formula I is the crystalline form of  claim 1 . 
       
     
     
       6. A crystalline form of compound of Formula I, 
       
         
           
           
               
               
           
         
         characterized by having X-ray powder diffraction pattern with peaks at diffraction angles 2θ of approximately 8.2°, 13.3°, 14.5°, 21.2°, and 26.6°±0.2°. 
       
     
     
       7. The crystalline form of  claim 6 , wherein the X-ray powder diffraction pattern further comprises peaks at diffraction angles 2θ of approximately 9.6°, 22.8°, and 25.4°±0.2°. 
     
     
       8. The crystalline form of  claim 6 , wherein the X-ray powder diffraction pattern is substantially in accordance with  FIG. 2 . 
     
     
       9. The crystalline form of  claim 6 , characterized by a melting point ranging from about 209° C. to 212° C. 
     
     
       10. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of Formula I, 
       
         
           
           
               
               
           
         
         and at least one pharmaceutically acceptable carrier, wherein at least 85% of the compound of Formula I is the crystalline form of  claim 6 . 
       
     
     
       11. A crystalline form of compound of Formula I, 
       
         
           
           
               
               
           
         
         characterized by having X-ray powder diffraction pattern with peaks at diffraction angles 2θ of approximately 6.2°, 17.8°, 22.0°, 26.2, and 26.9°±0.2°. 
       
     
     
       12. The crystalline form of  claim 11 , wherein the X-ray powder diffraction pattern further comprises peaks at diffraction angles 2θ of approximately 12.1°, 15.6°, and 28.9°±0.2°. 
     
     
       13. The crystalline form of  claim 11 , wherein the X-ray powder diffraction pattern is substantially in accordance with  FIG. 3 . 
     
     
       14. The crystalline form of  claim 11 , characterized by a melting point ranging from about 198° C. to 200° C. 
     
     
       15. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of Formula I, 
       
         
           
           
               
               
           
         
         and at least one pharmaceutically acceptable carrier, wherein at least 85% of the compound of Formula I is the crystalline form of  claim 11 . 
       
     
     
       16. A crystalline form of compound of Formula I, 
       
         
           
           
               
               
           
         
         characterized by having X-ray powder diffraction pattern with peaks at diffraction angles 2θ of approximately 11.3°, 12.4°, 20.3°, 21.4°, and 26.6°±0.2°. 
       
     
     
       17. The crystalline form of  claim 16 , wherein the X-ray powder diffraction pattern further comprises peaks at diffraction angles 2θ of approximately 15.0°, 17.9°, and 24.8°±0.2°. 
     
     
       18. The crystalline form of  claim 16 , wherein the X-ray powder diffraction pattern is substantially in accordance with  FIG. 4 . 
     
     
       19. The crystalline form of  claim 16 , characterized by a melting point ranging from about 204° C. to 207° C. 
     
     
       20. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of Formula I, 
       
         
           
           
               
               
           
         
         and at least one pharmaceutically acceptable carrier, wherein at least 85% of the compound of Formula I is the crystalline form of  claim 16 . 
       
     
     
       21. A crystalline form of compound of Formula I, 
       
         
           
           
               
               
           
         
         characterized by having X-ray powder diffraction pattern with peaks at diffraction angles 2θ of approximately 6.0°, 11.1° 17.7°, 24.1°, and 26.9°±0.2°. 
       
     
     
       22. The crystalline form of  claim 21 , wherein the X-ray powder diffraction pattern further comprises peaks at diffraction angles 2θ of approximately 8.8°, 11.9°, and 14.9°±0.2°. 
     
     
       23. The crystalline form of  claim 21 , wherein the X-ray powder diffraction pattern is substantially in accordance with  FIG. 5 . 
     
     
       24. The crystalline form of  claim 21 , characterized by a melting point ranging from about 190° C. to 193° C. 
     
     
       25. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of Formula I, 
       
         
           
           
               
               
           
         
         and at least one pharmaceutically acceptable carrier, wherein at least 85% of the compound of Formula I is the crystalline form of  claim 21 . 
       
     
     
       26. A crystalline form of compound of Formula I, 
       
         
           
           
               
               
           
         
         characterized by having X-ray powder diffraction pattern with peaks at diffraction angles 2θ of approximately 7.1°, 10.6°, 18.8°, 22.2° and 26.9°±0.2°. 
       
     
     
       27. The crystalline form of  claim 26 , wherein the X-ray powder diffraction pattern further comprises peaks at diffraction angles 2θ of approximately 9.4°, 16.5°, and 21.3°±0.2°. 
     
     
       28. The crystalline form of  claim 26 , wherein the X-ray powder diffraction pattern is substantially in accordance with  FIG. 6 . 
     
     
       29. The crystalline form of  claim 26 , characterized by a melting point ranging from about 200° C. to 203° C. 
     
     
       30. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of Formula I, 
       
         
           
           
               
               
           
         
         and at least one pharmaceutically acceptable carrier, wherein at least 85% of the compound of Formula I is the crystalline form of  claim 26 . 
       
     
     
       31. A crystalline form of compound of Formula I, 
       
         
           
           
               
               
           
         
         characterized by having X-ray powder diffraction pattern with peaks at diffraction angles 2θ of approximately 6.9°, 11.7° 15.1°, 21.1°, and 25.8°±0.2°. 
       
     
     
       32. The crystalline form of  claim 31 , wherein the X-ray powder diffraction pattern further comprises peaks at diffraction angles 2θ of approximately 7.5°, 19.3°, and 22.6°±0.2°. 
     
     
       33. The crystalline form of  claim 31 , wherein the X-ray powder diffraction pattern is substantially in accordance with  FIG. 7 . 
     
     
       34. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of Formula I, 
       
         
           
           
               
               
           
         
         and at least one pharmaceutically acceptable carrier, wherein at least 85% of the compound of Formula I is the crystalline form of  claim 31 . 
       
     
     
       35. A method for modulating HIF levels or HIF activity in a subject in need thereof comprising administering to the subject a pharmaceutical composition of  claim 26 . 
     
     
       36. A method of treating a disease, a disorder, or a condition associated with HIF level or HIF activity in a subject in need thereof comprising administering to the subject a pharmaceutical composition of  claim 26 , wherein the disease, disorder, or condition associated with HIF level or HIF activity is chosen from ischemia, anemia, wound healing, auto-transplantation, allo-transplantation, xeno-transplantation, systemic high blood pressure, thalassemia, diabetes, cancers, and inflammatory disorders.